Silica gel column chromatography, followed by HPLC purification on the apolar fraction of the methanol extract of marine sponge Theonella swinhoei, resulted in the isolation of a library of 10 polyhydroxylated steroids which we named theonellasterols B-H (1-7) and conicasterols B-D (8-10). The structures were determined on the basis of extensive spectroscopic data (MS, (1)H and (13)C NMR, COSY, HSQC, HMBC, and ROESY) analysis, and the putative binding mode to nuclear receptors (NRs) has been obtained through docking calculations. Pharmacological and structure-activity relationship analysis demonstrate that these natural polyhydroxylated steroids are potent ligands of human nuclear pregnane receptor (PXR) and modulator of farnesoid-X-receptor (FXR). In addition, the molecular characterization of theonellasterol G allowed the identification of the first FXR modulator and PXR ligand so far identified. Exposure of liver cells to this agent resulted in potent induction of PXR-regulated genes and modulation of FXR-regulated genes, highlighting its pharmacological potential in the treatment of liver disorders.
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http://dx.doi.org/10.1021/jm200169t | DOI Listing |
Mar Biotechnol (NY)
October 2024
School of Marine Biosciences, Kitasato University, Sagamihara, Kanagawa, 252-0373, Japan.
Numerous biologically active natural products have been discovered from marine sponges, particularly from Theonella swinhoei, which is known to be a prolific source of natural products such as polyketides and peptides. Recent studies have revealed that many of these natural products are biosynthesized by Candidatus Entotheonella phylotypes, which are uncultivated symbionts within T. swinhoei.
View Article and Find Full Text PDFSci Adv
July 2024
School of Zoology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.
Molybdenum is an essential micronutrient, but because of its toxicity at high concentrations, its accumulation in living organisms has not been widely demonstrated. In this study, we report that the marine sponge accumulates exceptionally high levels of molybdenum (46,793 micrograms per gram of dry weight) in a wide geographic distribution from the northern Red Sea to the reefs of Zanzibar, Indian Ocean. The element is found in various sponge body fractions and correlates to selenium.
View Article and Find Full Text PDFJ Biochem
September 2024
Department of Chemistry, Biology and Marine Science, Faculty of Science, University of the Ryukyus, 1-Senbaru, Nishihara, Nakagami, Okinawa 903-0213, Japan.
Given the continuous emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of new inhibitors is necessary to enhance clinical efficacy and increase the options for combination therapy for the coronavirus disease 2019. Because marine organisms have been a resource for the discovery of numerous bioactive molecules, we constructed an extract library of marine invertebrates collected from the Okinawa Islands. In this study, the extracts were used to identify antiviral molecules against SARS-CoV-2.
View Article and Find Full Text PDFInt J Syst Evol Microbiol
November 2023
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, PR China.
A novel bacterial strain, designated as PHS-Z3, was isolated from a marine sponge belonging to the genus on the Puerto Galera Deep Monkey, Philippines. Cells of PHS-Z3 were Gram-stain-positive, motile, oxidase- and catalase-positive, white-pigmented, spore-forming, short rods that could grow at 10-40 °C (optimum, 20 °C), pH 6.0-9.
View Article and Find Full Text PDFPNAS Nexus
March 2022
Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
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